Ginsenoside-Rh2 treatment modulates the protein level of p21 and cyclin D, which results in a marked reduction in proliferation on MCF-7 human breast cancer cells [16]. Ginsenoside-Rh2 also induces apoptosis through the activation of p53 and the increase of the proapoptotic regulator, Bax, in colorectal cancer cells [37]. In addition, Ginsenoside-Rh2 markedly inhibits the viability of breast cancer cells (MCF-7 and MDA-MB-231) with G1 phase cell cycle arrest, which is caused by p15 Ink4B and p27 Kip1-dependent inhibition of

cyclin-dependent kinases [10]. Although many selleck chemicals studies describing the anticancer effect of ginsenoside-Rh2 have been conducted, much of its mechanism relating to anticancer activities remains unclear. AMPK is a pleiotropic kinase that selleckchem signals for both survival and apoptosis of cells. It plays a key role as a regulator of cellular energy homeostasis [39]. The kinase is activated in response to ATP depletions, such as those of glucose starvation, hypoxia, ischemia, and heat shock. Moreover, a proapoptotic function of AMPK was also reported, where the connection of AMPK with several tumor suppressors suggests that AMPK is a mediator of apoptosis. The LKB1 tumor suppressor that mutated in Peutz–Jeghers syndrome directly phosphorylates and activates AMPK [40] and [41]. The TSC2 tumor suppressor is directly phosphorylated by AMPK, and the AMPK-mediated phosphorylation of

TSC2 has an important role in cell survival [42] and [43]. The present study focuses on identifying the mechanism that underlies the anticancer activity of ginsenoside-Rh2. In this study, we show that in HepG2 cells treated with ginsenoside-Rh2, AMPK activity is increased in a time- and dose-dependent manner (Fig. 3 and Fig. 4). To confirm the role of AMPK in ginsenoside-Rh2-induced apoptosis, HepG2 cells were treated with ginsenoside-Rh2,

and were then assessed for the degree of apoptosis according to the degree of variation in AMPK activity. In this study, we have shown that AMPK activity is caused by ginsenoside-Rh2-mediated ROS generation (Fig. 5), and that it contributes to cancer cell growth and survival under treatment with ginsenoside-Rh2 Interleukin-2 receptor (Fig. 4). These observations indicate that AMPK can function as an antiapoptotic molecule. It is well documented that MAPK pathways modulate gene expression, mitosis, proliferation, metabolism, and apoptosis. Previous studies have demonstrated that MAPK signaling is involved in ginsenoside-mediated anticarcinogenesis. Ginsenoside Rg3 and Rh2 inhibit the proliferation of prostate cancer cells by modulating MAPK [17]. Ginsenoside Rb1 inhibits histamine release and IL-4 production induced by substance P, a neurotransmitter, via the ERK pathway [44]. A ginseng saponin metabolite, compound K, suppresses phorbol ester-induced matrix metalloproteinase-9 expression through the inhibition of MAPK signaling in human astroglioma cells [45].